When I first went into pathology, cancer was thought of as a phenomenon—often caused by mysterious carcinogens—that arises "de-novo" out of a background of normal cells. Fortunately, from a diagnostic point of view, cancer cells are demonstrably different from benign cells under the microscope. Also, in the case of some cancers [cancer of the cervix is an excellent example] cells oftentimes show a morphologic sequence from benign to patently malignant. Now, to my way of thinking, this presents a contradiction. How can cancer cells arise "suddenly" out of a benign background if some [most?] cancers show an identifiable pre-cancerous stage?

The answer is clear. Benign cells go through a series of changes before becoming frankly malignant. In that cancer cells are genetically altered mutants, it follows that the pre-cancerous cells are also genetically altered but not altered enough to produce the invasion and metatastases that are characteristic of cancer. Therefore pre-cancer is characterized by multiple mutations culminating in cancer.

How can this happen? In some ways life itself is a carcinogenic event. The body is composed of trillions of cells and, during the course of an average lifespan, there may be as many as 10 to the 18th power mitoses (cell divisions)—10,000,000,000,000,000,000 mitoses. It is extremely important that the daughter cells of each mitosis have exactly the same chromosomal complement as their maternal cell. Consequently, each cell has multiple fail-safe mechanisms built into the genome to insure that there is no genetic experimentation.

Nothing is perfect though. Inevitably the occasional mitosis goes wrong and produces genetically altered daughter cells. Why? In some cases this may be purely random and accidental. In other cases—possibly most cases—this may be the result of long term, accelerated cell division. Accelerated cell division can be caused by hormonal hyperstimulation or, perhaps more often, by long-term chronic inflammation. The more cell divisions the more chances for genetic error—simple mathematics. Also, in cases in which the cells are forced to hyper-reproduce, the basic chemical building blocks of reproduction may become locally deficient—genetic error becomes more probable. In a few cases, mutagens [chemical or physical agents that produce mutation] may play a roll. Oftentimes, several factors are involved.

Tobacco addiction, for example, is associated with an increased incidence of cancer, especially of the respiratory system. Chronic inflammation of the mouth, throat and bronchi kills lining cells forcing the basal [stem] cells to divide at an increased rate. The likelihood of mutation is increased based on 1] long term exposure to cell damaging chemicals 2] compensatory increased cell division 3] "stressed" cell divisions and possibly 4] the mutagenic effect of some of the components of tobacco smoke. In some cases a fifth factor may be involved—heredity. It is likely that some of us have inherited genomes from our fathers and/or mothers that already have defective genes that could—if additional mutations occur—lead to cancer.

This doesn't explain cancer in-and-of itself because, as I previously wrote, cancer is usually a multistep process. An individual mutation—unless at an extremely critical point of the genome—won't produce cancer. A series of less critical mutations—which may occur during long-term irritation/inflammation— are more likely to interfere with the cell's ability to gauge its reproductive activity and relationship to other cells accurately, producing the hypermitotic, aggressive growth that we call cancer.

Even though there are factors that increase the risk of mutation and cancer, it must be remembered that even in "high-risk" situations, mutation is a random event, which explains why most individuals don't develop cancer during the course of a normal life span. Should we live for hundreds of years, however, it is predictable that every one of us would develop multiple cancers in virtually every organ. Example: There is a tiny risk of lung cancer even in individuals without exposure to tobacco smoke. At the same time, most chronic smokers escape lung cancer. It's not the way to bet, however. Lung cancer in smokers is reportedly ten times more frequent in non-smokers. Even this statistic probably minimizes the risk. I've spoken to dozens of people dying of primary lung cancer and every one—without exception—was a smoker. Still, even in high-risk individuals, the chance of completing the malignant sequence is quite random but the probabilities are heavily weighted to one side. No one is immune from cancer and never bet against the house. Surely this must be the case with many cancers. Gastric carcinoma is heavily associated with the presence of the bacterium, Helicobacter pylorii, an infective organism that produces gastritis and gastric ulcers. Still, many people with gastric cancer show no evidence of this bacterium probably because gastric cancer is caused by chronic gastritis and H. pylorii is only one of many causes of chronic gastritis.

Does my theory explain all cancers? Probably not. Most cases of infantile and childhood cancer defy explanations of long term cell stimulation. Still, even these cancers are the products of cellular genetic aberrations and, the majority of these cancers occur in tissues with rapidly dividing cells. In some cases—retinoblastoma being the classic example—the child inherits a defective gene and it requires at least one additional mutation to produce full-blown retinal cancer. The additional mutation may be purely random. It is possible that some cases of cancer are due to the pure randomness of mutation occurring during normal cell division which could well explain the rarity of most childhood cancers. The vast majority of children haven't lived long enough to complete a malignant sequence. Of course, an inherited gene mutation may place both children and adults one step closer to developing cancer.

Trace "carcinogens"—cosmic rays, gamma rays, microwaves, chemicals—in our food, air and water, despite all the hype, play only a minor roll in most cancers. The more common causes are, in fact, so common that avoidance of risk is difficult i.e. chronic colitis and colon cancer; chronic pancreatitis and pancreatic cancer; chronic sun exposure and skin cancer; chronic estrogen hyperstimulation and uterine cancer etc. As Pogo said, "We have met the enemy and he is us."